Systems, devices, and methods for localized drug delivery

ABSTRACT

Devices, systems, and methods for localized drug delivery. In at least one embodiment of a method of localized drug delivery, the method comprises the steps of placing a resorbable device within a tube, introducing the tube within a mammalian body at or near a tissue and/or organ within the mammalian body, and anchoring the resorbable device to the tissue and/or organ. Devices and systems useful for performing such a method are also disclosed herein, wherein an exemplary device comprises at least one drug release portion having at least one drug to be released over time and a binder intermixed with the at least one drug, and at least one resorbable anchor portion coupled to the at least one drug release portion.

PRIORITY

The present application is related to, claims the priority benefit of,and is a continuation application of, U.S. patent application Ser. No.12/579,125, filed on Oct. 14, 2009 and issued as U.S. Pat. No. 8,535,260on Sep. 17, 2013, which is related to, and claims the priority benefitof, U.S. Provisional Patent Application Ser. No. 61/105,510, filed Oct.15, 2008. The contents of each of these applications and patent arehereby incorporated by reference in their entirety into this disclosure.

BACKGROUND

Medications traditionally have been administered in various ways,including orally, subcutaneously, intramuscularly, or intravenously.Other drug delivery systems include transdermal patches,membrane-encased cells genetically engineered to secrete a desired drug(e.g., nerve growth factor or insulin), and slow-release drug systems.Traditional routes of administration require patients to actively followdosing instructions, for example, when medication is administeredorally, such as an antibiotic, hormone, or vitamin, or when repeatedvisits to the doctor are necessary because the route of administrationis by injection. These methods of administration are especiallyproblematic in cases where the patient is a child, elderly, or where themedication must be administered on a chronic basis. Generally,compliance with taking medication is a problem for many adults as theysimply forget to take it as recommended or required.

Transdermal patches are used currently to administer drugs such ashormones, estrogen, nicotine, and nitroglycerin (for angina or chestpain). While such a system has been shown to be effective in certaininstances, a drug must penetrate the skin barrier in order to beadministered via a transdermal patch. Many drugs cannot be administeredin effective amounts transdermally. Other slow-release delivery systemsare useful, but they require the removal of the matrix itself after thedrug has been completely absorbed. Hence, surgery is required to insertthe composition and to remove the exhausted matrix from the patient.

Since the sustained release of biological agents was established severaldecades ago, the sustained release has been advanced by controlling thediffusion of drugs through polymeric matrices and/or the degradation ofthese polymers. Recently, drug release in proportion to internal orexternal stimuli has become recognized, which can be achieved by usingstimuli-responsive polymeric materials. Many of these polymers achievetheir functions by changes in temperature, pH, glucose concentration,and the release of ribosomal enzymes. Biodegradable polymers have greatpotential for applications as implantable carriers for drug deliverysystems. With an auto-feed-back drug delivery system, severalphysiological changes in a living body can be utilized as the signalinducing polymer degradation and subsequent drug release.

The sustained delivery of antibiotic pharmaceutical agents is oftendesirable for the treatment of intractable fungal and bacterialinfections. Methods of slow drug release have considerablepharmacodynamic advantages over long-term intravenous drug therapy. Theformer may result in shorter hospitalizations and greater degrees ofcompliance, and may eliminate the need for indwelling catheters. Slowdrug release is usually achieved either by incorporation of atherapeutic drug into an implantable reservoir or by implantation ofbiodegradable materials containing the desired drug. The development ofbiodegradable antimicrobial compounds is particularly appealing for thetreatment of postsurgical infections and of focal infections inimmuno-compromised patients. Efficacies of slow drug release systems areusually determined by measurement of concentrations of the implanteddrug in plasma or by assessment of the underlying disease treated (e.g.,improving infection or decrease in the size of cancer, etc.).

For chronic heart problems, slow drug release with therapeutic factorshaving angiogenic, myogenic, and antiarrhythmic potential is veryimportant. The local drug release avoids using larger concentrations ordoses to avoid systemic effects. The disclosure of the presentapplication introduces devices, systems, and methods by which implants(biological, chemical or electrical) can be delivered to a tissue and/ororgan to provide long term therapeutics.

BRIEF SUMMARY

In at least one embodiment of a device for localized drug delivery ofthe present disclosure, the device comprises at least one drug releaseportion comprising at least one drug to be released over time and abinder intermixed with the at least one drug, wherein the binder isbiologically degradable within a mammalian body at a first rate ofdegradation, and also comprises at least one resorbable anchor portioncoupled to the at least one drug release portion, wherein the at leastone resorbable anchor portion is biologically degradable within themammalian body at a second rate of degradation, wherein the second rateof degradation is slower than the first rate of degradation. In anexemplary embodiment, and when the device is anchored to a tissue ororgan within the mammalian body, as the binder degrades and the at leastone drug is released into the mammalian body, the at least oneresorbable anchor portion maintains its anchored position within thetissue or organ. In another embodiment, wherein when the device ispositioned within the mammalian body, as the binder degrades at thefirst rate of degradation the at least one drug is released into themammalian body.

In at least one embodiment of a device for localized drug delivery ofthe present disclosure, the device comprises a configuration selectedfrom the group consisting of a pin configuration, a hook-pinconfiguration, and a chip configuration. In an additional embodiment,the at least one resorbable anchor portion comprises at least one barband at least one point-tip. In yet another embodiment, the at least oneresorbable anchor portion comprises at least one coil. In at least oneembodiment, the tissue or organ within the mammalian body comprises amammalian heart.

In at least one embodiment of a system for localized drug delivery ofthe present disclosure, the system comprises a tube having a proximalend and a distal end, the tube defining a first opening at the proximalend and a second opening at the distal end, the tube sized and shaped tofacilitate placement of a resorbable device within a mammalian body bydelivering the resorbable device from the second opening of the tube toa location within the mammalian body, and the resorbable devicecomprising at least one drug release portion and at least one resorbableanchor portion intermixed with the at least one drug release portion. Inanother embodiment, the system further comprises a shaft positionedwithin the tube, the shaft having a longitudinal axis, a proximal end,and a distal end, wherein the shaft is operable to facilitate placementof the resorbable device within the mammalian body. In yet anotherembodiment, the system further comprises an embolus positioned at ornear the distal end of the shaft, wherein the embolus is sized andshaped to facilitate placement of the resorbable device within themammalian body. In an additional embodiment, the shaft is rotatableabout its longitudinal axis, and wherein the rotation of the shaft isoperable to facilitate placement of the resorbable device within themammalian body.

In at least one embodiment of a system for localized drug delivery ofthe present disclosure, the system further comprises a spring positionedat or near the distal end of the shaft between the shaft and theembolus, the spring capable to facilitate placement of the resorbabledevice within the mammalian body. In another embodiment, the systemfurther comprises an embolus positioned at or near the distal end of theshaft, wherein the embolus is sized and shaped to facilitate placementof the resorbable device within the mammalian body. In an additionalembodiment, the introduction of a gas at or near the proximal end of thetube facilitates placement of the resorbable device within the mammalianbody.

In at least one embodiment of a system for localized drug delivery ofthe present disclosure, the tube comprises an engagement catheter. In atleast one embodiment, the engagement catheter comprises a suctionengagement steering catheter. In another embodiment, the suctionengagement steering catheter comprises a skirt positioned at the distalend of the suction engagement steering catheter, the skirt operable toreversibly engage a tissue or organ within the mammalian body tofacilitate placement of the resorbable device within the mammalian body.In at least one embodiment, the at least one drug release portioncomprises at least one drug to be released over time and a binderintermixed with the at least one drug, the binder biologicallydegradable within a mammalian body at a first rate of degradation, andwherein the at least one resorbable anchor portion is biologicallydegradable within the mammalian body at a second rate of degradation,the second rate of degradation being slower than the first rate ofdegradation.

In at least one embodiment of a method for localized drug delivery ofthe present disclosure, the method comprises the step of positioning aresorbable device of the present disclosure within a mammalian body,wherein the resorbable device comprises at least one drug releaseportion comprising at least one drug to be released over time and abinder intermixed with the at least one drug, and further comprising atleast one resorbable anchor portion coupled to the at least one drugrelease portion. In at least one embodiment, the step of positioning theresorbable device within the mammalian body comprises the steps ofplacing the resorbable device within a tube, introducing the tube withinthe mammalian body at or near a tissue or organ within the mammalianbody, and anchoring the resorbable device to the tissue or organ. Inanother embodiment, the step of anchoring the resorbable device to thetissue or organ is performed using a shaft positioned within the tube.In yet another embodiment, the step of anchoring the resorbable deviceto the tissue or organ is performed using a gas from a gas sourceintroduced into the tube to facilitate placement of the resorbabledevice. In an additional embodiment, the tissue or organ within themammalian body comprises a mammalian heart.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a block diagram of an exemplary composition of at leastone embodiment of a resorbable device according to the presentapplication;

FIG. 1B shows a block diagram of another exemplary composition of aresorbable device according to the present application;

FIGS. 2A and 2B show exemplary embodiments of resorbable devicesaccording to the present application having a pin configuration;

FIG. 2C shows an exemplary embodiment of a resorbable device accordingto the present application having a hook-pin configuration;

FIG. 2D shows an exemplary embodiment of a resorbable device accordingto the present application having a chip configuration;

FIG. 2E shows an exemplary embodiment of a resorbable device accordingto the present application having a coiled resorbable anchor portion;

FIGS. 3A and 3B show cross-sectional views of an exemplary embodiment ofa delivery system according to the present application having a tube, ashaft, a spring, and an embolus, wherein the delivery system is used toposition a resorbable device at a tissue and/or organ;

FIG. 3C shows a cross-sectional views of an exemplary embodiment of adelivery system according to the present application having a tube, ashaft, a spring, and an embolus, wherein the delivery system has anotable curvature useful to facilitate positioning a resorbable deviceat a tissue and/or organ;

FIGS. 4A and 4B show cross-sectional views of an exemplary embodiment ofa delivery system according to the present application having a tube, ashaft, and an embolus, wherein the delivery system is used to position aresorbable device at a tissue and/or organ;

FIGS. 5A and 5B show cross-sectional views of an exemplary embodiment ofa delivery system according to the present application having a tube andan embolus, wherein the delivery system is used to position a resorbabledevice at a tissue and/or organ using a gas;

FIGS. 6A and 6B show cross-sectional views of an exemplary embodiment ofa delivery system according to the present application having a tube, ashaft, and an embolus, wherein the delivery system is used to position aresorbable device at a tissue and/or organ by rotating the shaft aboutits longitudinal axis;

FIG. 7 shows a cross-sectional view of an exemplary embodiment of adelivery system according to the present application having anengagement catheter with an optional skirt, a shaft, and an embolus,wherein the delivery system is used to position a resorbable device at atissue and/or organ;

FIG. 8A shows an exemplary embodiment of a resorbable device of thepresent application having a hook-pin configuration positioned at atissue and/or organ;

FIGS. 8B and 8C show cross-sectional views of an exemplary embodiment ofa delivery system according to the present application having a tube, ashaft, and an embolus, wherein the delivery system is used to position aresorbable device having a hook-pin configuration at a tissue and/ororgan;

FIG. 9A shows an exemplary embodiment of a resorbable device accordingto the present application having a chip configuration;

FIG. 9B shows an exemplary embodiment of a resorbable device accordingto the present application having a chip configuration positioned at atissue and/or organ;

FIG. 9C shows a cross-sectional view of an exemplary embodiment of adelivery system according to the present application having a tube, ashaft, and an embolus, wherein the delivery system is used to position aresorbable device having a chip configuration at a tissue and/or organ;

FIG. 10A shows an exemplary embodiment of a resorbable device accordingto the present application positioned at a tissue and/or organ;

FIG. 10B shows an exemplary embodiment of a resorbable device accordingto the present application positioned at a tissue and/or organ whereinthe drug release portion of the resorbable device has start tobiologically degrade allowing the release of drug;

FIG. 10C shows an exemplary embodiment of a resorbable device accordingto the present application positioned at a tissue and/or organ whereinthe drug release portion has completely biologically degraded;

FIG. 10D shows an exemplary embodiment of a resorbable device accordingto the present application positioned at a tissue and/or organ whereinthe resorbable anchor portion of the resorbable device has start tobiologically degrade;

FIG. 10E shows an exemplary embodiment of a resorbable device accordingto the present application positioned at a tissue and/or organ whereinthe drug release portion and the resorbable anchor portion have bothcompletely biologically degraded;

FIG. 11A shows an exemplary embodiment of a delivery system according tothe present application used to position a resorbable device within aheart;

FIG. 11B shows an exemplary embodiment of a resorbable device accordingto the present application positioned at a heart septum; and

FIG. 12 shows a block diagram of an exemplary method of positioning aresorbable device within a body according to the present application.

DETAILED DESCRIPTION

The disclosure of the present application provides various devices andsystems for localized drug delivery and methods for using the same. Forthe purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of this disclosure is thereby intended.

The devices, systems, and methods of the disclosure of the presentapplication allow patients to receive medications in a slow-release,self-absorbing/resorbable form at various time intervals, for example,from days to weeks to months. In at least one embodiment, one or moredrugs may be released at intervals of about one month, depending on therate of absorption of the associated matrix. Exemplary devices of thepresent disclosure may be used as an implantable, slow-release,self-absorbing pharmaceutical composition containing one or more activeagents in combination with a biologically-compatible, self-absorbingmatrix useful to deliver the pharmaceutical composition to thebloodstream and/or directly to a bodily tissue and/or organ. Suchdevices may also be a pacemaker-type device or similar electronics totransmit electrical therapy (pacing, resynchronization ordefibrillation) chronically and as needed. As referenced herein, theterms “self-absorbing” and “resorbable” refer to properties of variousdevices which are biologically absorbable within a mammalian body asdescribed in further detail herein.

The disclosure of the present application discloses devices providing animplantable pharmaceutical composition containing the active substancein a biologically-compatible, self-absorbing matrix. Further, thedisclosure of the present application provides an implantation devicefor implanting such pharmaceutical compositions in various bodilytissues including, for example, myocardial muscle. In at least someembodiments of a device of the disclosure of the present application,the device comprises a slow-release, self-absorbing, pharmaceuticalcomposition containing one or more active agents in combination with abiologically-compatible, self-absorbing matrix to treat patients withcongestive heart failure (using, for example, various beta blockers,anticalcic agents, and/or cardiotonic drugs), coronary vasodilators inpatients with refractory angina, anti-arrhythmic drugs, pulmonaryvasodilators (PG1) to treat primary pulmonary hypertension,anticoagulation therapy (using, for example, fibrinolitics and/orantiadhesive platelets treatment), antibiotics for chronic fungal orbacterial cardiac infections or pulmonary infections (e.g., cysticfibrosis lung disease), and anti-rejection drugs (heart transplants),for example.

In addition to the foregoing, there are particular sites within themyocardium which may benefit from local drug release therapy. Examplesinclude ischemic sites and arrhythmogenic sites for localized use offibrinolitic or anticoagulation therapy or vasodilators. The localdelivery of agents within such tissues will minimize the dilution ofagents and decrease the possibility of the agents being delivered toinappropriate sites. This localized delivery is important, for example,for antiarrhythmic agents whose pro-arrhythmia systemic effects havebeen well recognized.

In at least one embodiment of a system and/or device of the presentapplication, the system and/or device comprises an engagement-suctioncatheter that can deliver drugs to specific and precise “target” withinthe heart or other organ(s) and/or tissue(s). The disclosure of thepresent application is intended for minimally invasive delivery ofagents for the treatment of medical conditions, for example, thoseconditions in the heart or adjacent veins and arteries where precisioninjection of genes or other agents is required in the treatment of thepatient. Available epidemiologic, pharmacologic, and clinico-therapeuticevidence demonstrates how the chronobiologic approach to ischemic heartdisease can contribute new insight and opportunities to improve drugdesign and drug delivery to enhance therapeutic outcomes. In at leastone embodiment of a device, system, or method of the present disclosure,an objective is to make drug delivery to the endocardial surface of theheart very specific and precise.

At least one embodiment of a device of the present application is shownin the block diagram of FIG. 1A. As shown in FIG. 1A, an exemplarydevice (generally referred to herein as a resorbable device 100)comprises at least two components, namely a drug release portion 102 anda resorbable anchor portion 104. Drug release portion 102, in order tofacilitate the delivery of a drug over time as described herein, isconfigured so that a drug is capable of at least localized deliverywithin a patient's body after resorbable device 100 has been implantedtherein. For purposes of the present disclosure, a “drug” shall mean atleast one of any number of therapeutics, pharmaceuticals, vitamins,antibiotics, hormones, and the like. The disclosure of the presentapplication does not intend for the term “drug” to be limited to, forexample, a prescription medication.

Drug release portion 102 may comprise any number of configurations forthe release of a drug over time. For example, drug release portion 102may comprise a drug combined with a binder/filler, whereby as thebinder/filler breaks down over time within the body, the drug isreleased over time. Drug release portion 102 may comprise, for example,a biologically-compatible, resorbable matrix that biodegrades over timeonce positioned within a patient's body. Drug release portion 102 mayalso comprise a drug positioned within a biodegradable shell, whereinthe drug may be released within a body as the biodegradable shelldegrades, is absorbed, or is digested within a body.

In the exemplary embodiment of a resorbable device 100 shown in theblock diagram of FIG. 1B, resorbable device 100 comprises a drug releaseportion 102, wherein drug release portion 102 comprises a drug portion106 and a binder 108 either bound to and/or around drug portion 106,whereby the use of the binder 108 allows the drug within drug portion106 to be released, for example, within the blood stream, as binder 108breaks down within the body. In such an exemplary embodiment, drugportion 106 and binder 108 are intermixed with one another to facilitatethe time-release of drug portion 106 as referenced herein.

To facilitate the “anchoring” of resorbable device 100 within the body,resorbable device 100 comprises a resorbable anchor portion 104.Exemplary embodiments of resorbable devices 100 of the disclosure of thepresent application are shown FIGS. 2A-2E. In the exemplary embodimentof a resorbable device 100 shown in FIG. 2A, resorbable device 100 has a“pin” configuration, whereby the pin 200 is sized and shaped forplacement within the body in, for example, cardiac tissue or one or moreother bodily organs, such as digestive, respiratory, and/or urinarytracts. In such an embodiment, and as with additional embodimentsreferenced herein, the pin 200 (or other form of a resorbable device100) may be anchored within the body for a period of time to allow forat least some drug delivery over time from the drug release portion 102.In the exemplary embodiment shown in FIG. 2A, resorbable device 100comprises a partially-round drug release portion 102 and a resorbableanchor portion 104 having barbs 202 to facilitate anchoring within abody as described herein. FIG. 2B shows another exemplary embodiment ofa resorbable device 100 in having a pin 200 configuration, wherein thedrug release portion 102 is substantially round and wherein the pin 200has a point tip 204 allowing resorbable device to be positioned within abody. As referenced herein, various additional embodiments and/orconfigurations of pins 200 may comprise any number of shapes, componentsand/or features, including, but not limited to, barbs 202 and/or pointtip 204.

Additional exemplary embodiments of a resorbable device 100 of thedisclosure of the present application are shown in FIGS. 2C-2E. FIG. 2Cshows an embodiment of a resorbable device 100 with a natively curvedconfiguration, whereby resorbable device 100 may be anchored within abody using two resorbable anchor portions 104 to allow drug releaseportion 102 to release drug over time. Anchor portion 104 may compriseany number of attributes as referenced herein in connection with otheranchor portions 104, including, but not limited to, barbs 202 and/orpoint tip 204. Placement of such an embodiment within a body is shown inFIGS. 8B and 8C.

FIG. 2D shows an embodiment of a resorbable device 100 in “chip” form,wherein the drug release portion 102 comprises a chip 206, and whereinone or more resorbable anchor portions 104 facilitate the anchoring ofresorbable device 100 within a body. Chip 206 may also comprise, forexample, a microchip and/or one or more other mechanisms to facilitate aprogrammed delivery of drug over time. In addition, a resorbable device100 having a chip 206 configuration, or another configuration of aresorbable device 100 of the present disclosure sized and shaped toallow for the positioning of a microchip thereon, may be or functionsimilar to various electrical stimulating pacemakers or other types ofelectronics to transmit electrical therapy chronically and/or as needed.For example, and in at least one embodiment of a resorbable device 100of the present disclosure, resorbable device 100 comprises a chip 206configuration as shown in FIG. 2D, wherein the chip 206 comprises amicrochip.

FIG. 2E shows an exemplary embodiment of a resorbable device 100 wherebythe resorbable anchor portion 104 comprises a screw-like configuration(a coil screw 208 with a single or double helix, for example), wherebythe resorbable device 100 may be screwed into position as described inFIGS. 6A and 6B. Additional embodiments and configurations of resorbabledevice 100 comprising a drug release portion 102 and a resorbable anchorportion 104 as referenced herein are contemplated to be within the scopeof the present application.

A cross-sectional view of an exemplary system for positioning aresorbable device within a body is shown in FIGS. 3A and 3B. As shown inFIG. 3A, exemplary delivery system 300 comprises a delivery tube 302 anda shaft 304 slidingly engaged within delivery tube 302. Shaft 304, whenmoved in a direction as shown by arrow 314 in FIG. 3B, exerts pressureon a spring 306 which, in turn, exerts a pressure on an embolus 308 tofacilitate delivery of resorbable device 100 (shown having a pin 200configuration in FIGS. 3A and 3B). As shown in FIG. 3B, when shaft 304moves in the direction shown by arrow 314, resorbable device 100 may beimplanted into tissue and/or organ 310, with the surface of tissueand/or organ 310 shown in FIGS. 3A and 3B. In an embodiment of aresorbable device 100 wherein resorbable device 100 comprises barbs 202and/or a point tip 204 (as shown in FIGS. 2A, 2C, and 2D), point tip 204may puncture tissue and/or organ 310 to facilitate anchoring ofresorbable device 100 therein, and/or barbs 202 may physically engagetissue and/or organ 310 to prohibit removal of resorbable device 100after it is anchored.

As shaft 304 slides within tube 302, embolus 308 facilitates thedelivery of resorbable device 100 as shown in FIG. 3B. Embolus 308 maybe prevented from exiting tube 302 by, for example, the use of one ormore embolus stop bars 312 as shown in FIGS. 3A and 3B. Furthermore,embolus 308 (and/or portions of shaft 304 as described below) may besized and shaped so that a resorbable device 100 may be removablyengaged thereto and subsequently delivered to a target area within abody as described herein.

Exemplary resorbable devices 100 of the disclosure of the presentapplication may be positioned in or onto any number of tissues and/ororgans 310, including, but not limited to, heart tissue, muscle, thebrain, and the lungs. Such resorbable devices 100, when positionedwithin a tissue and/or organ 310, should not be positioned so deeply asto cause potential hemorrhage and/or filtration of a vascular bed. In atleast one embodiment, resorbable devices 100 may be delivered to atarget tissue and/or organs using any number of delivery systems 300 ofthe present disclosure, with the various delivery systems 300 configuredfor a particular application. For example, an exemplary delivery system300, such as delivery system 300 shown in FIGS. 3A and 3B, may be usedto deliver resorbable devices 100 to a tissue or organ having a surfacerelatively perpendicular to the direction of entry of the deliverysystem 300. As shown in FIG. 3A, for example, the distal end 316 ofdelivery system 300 is relatively perpendicular to tissue and/or organ310, whereby such a configuration of delivery system 300 is suitable todeliver a resorbable device 100 of the present disclosure. In at leastanother embodiment, and as shown in the cross-sectional view of anexemplary system for positioning a resorbable device within a body shownin FIG. 3C, delivery system 300 has a notable curvature to facilitatedelivery of resorbable device 100 to a tissue and/or organ 310relatively parallel to the direction of entry of delivery system 300into the body.

Additional cross-sectional views of exemplary embodiments of deliverysystems 300 of the disclosure of the present application are shown inFIGS. 4A and 4B. As shown in the embodiment shown in FIG. 4A, deliverysystem 300 comprises tube 302, shaft 304, and embolus 308. In thisexemplary embodiment, delivery system 300 does not comprise a spring306, and use of the system (by sliding shaft 304 in the direction ofarrow 400 shown in FIG. 4B towards the distal end of tube 302) deliversa resorbable device 100 as previously described herein. In the exemplaryembodiment shown in FIG. 4B, delivery system 300 comprises a tube 302and a shaft 304, whereby resorbable device 100 may be positioned usingonly shaft 304. The embodiments of delivery system 300 as shown in FIGS.3A-4B are exemplary in nature, and other mechanical embodiments ofdelivery systems 300 operable to deliver resorbable devices 100 asreferenced herein are considered to be within the scope of the presentapplication.

An cross-sectional view of an exemplary embodiment of a delivery system300 of the disclosure of the present application utilizing pressurizedgas is shown in FIGS. 5A and 5B. As shown in FIGS. 5A and 5B, deliverysystem 300 comprises a tube 302, an embolus 308, and a resorbable device100. The delivery of a gas from a gas source (not shown) may, as shownin FIG. 5B, cause embolus 308 and resorbable device 100 to move in thedirection shown by arrows 500, 502 so that resorbable device 100 may bepositioned within a tissue and/or organ 310. Carbon dioxide (CO.sub.2)is shown as being the gas in this exemplary embodiment, but any numberof various gases may be used to accomplish the same. Additionally, oneor more fluids (water, saline, etc.) may be used either in place of, orin addition to, one or more gases to facilitate delivery of resorbabledevice 100.

A cross-sectional view of an additional embodiment of a delivery system300 of the disclosure of the present application is shown in FIGS. 6Aand 6B. As shown in FIGS. 6A and 6B, delivery system 300 comprises atube 302 and a shaft 304 where shaft 304 is capable of rotation aboutits longitudinal axis as shown in FIG. 6B. Shaft 304 is eitherpermanently or removably coupled to embolus 308 and is sized and shapedto facilitate delivery of resorbable device 100. Resorbable device 100may be positioned at or near a tissue and/or organ 310 by moving shaft304 in a direction of arrow 600 shown in FIG. 6A. When resorbable deviceis positioned at or near tissue and/or organ 310, shaft 304 may berotated about its longitudinal axis as shown by arrow 602 in FIG. 6B,causing resorbable device 100 (having a resorbable anchor portion 104comprising a screw-like configuration as shown, for example, in FIG. 2E)to be screwed into position within tissue and/or organ 310.

FIG. 7 shows a cross-sectional view of an embodiment of a deliverysystem 300 of the disclosure of the present application wherein suctionfacilitates the delivery of resorbable device 100. As shown in theexemplary embodiment shown in FIG. 7, delivery system 300 comprises anengagement catheter 700 and shaft 304 positioned therein, wherein themovement of shaft 304 within engagement catheter 700, similar to themovement of shaft 304 within tube 302 in other embodiments referencedherein, facilitates the positioning of resorbable device 100 within atarget tissue and/or organ 310. Engagement catheter 700 may comprise anynumber of engagement catheters capable of reversibly attaching to atarget tissue and/or organ 310 as shown in FIG. 7. In at least onepreferred embodiment, engagement catheter 700 comprises a suctionengagement steering catheter, wherein said catheter may be inserted intoa body to a particular target site for delivery of resorbable device100. In such an embodiment, engagement catheter 700 may be referred togenerally as a delivery catheter if it facilitates the placement, ordelivery, of a resorbable device 100.

In the exemplary embodiment shown in FIG. 7, delivery system 300 furthercomprises an embolus 308 sized and shaped to facilitate the delivery ofresorbable device 100. In addition, and as shown in this exemplaryembodiment, engagement catheter 700 may optionally comprise a skirt 702coupled to the distal end of engagement catheter 700, allowingengagement catheter 700 to engage a larger surface area of a tissueand/or organ 310 as would otherwise be possible without such a skirt702. Engagement catheter 700 may reversibly attach to a tissue and/ororgan 310 using suction from a suction source (not shown) operablycoupled to the engagement catheter 700 at or near the proximal end ofthe engagement catheter 700.

Another cross-sectional view of an embodiment of a delivery system 300of the disclosure of the present application is shown in FIGS. 8B and8C. As shown in FIGS. 8B and 8C, delivery system 300 comprises anengagement catheter 700 (shown with an optional skirt 702), a shaft 304,and an embolus 308, whereby delivery system 300 is operable to deliverresorbable device 100 to a target tissue and/or organ 310 in thedirection of arrows 800, 802. In the exemplary embodiment shown in FIGS.8A-8C, resorbable device 100 has a hook-pin configuration (similar tothe configuration shown in FIG. 2C), and in this particular embodiment,resorbable device 100 comprises a “memory” whereby its natural/nativeconfiguration is a hook configuration (as shown in FIG. 8A), which canbe temporarily bent into a relatively open position for implantation asshown in FIGS. 8B and 8C). Materials having such a memory suitable forvarious resorbable devices of the present disclosure include, but arenot limited to, polymers derived from polylactic-co-glycolic acid)(PLGA) including various copolymers, graft copolymers, interpenetratingnetworks (IPNS), dipalmitylphosphatidylcholine, chondroitin sulfate A,polylactic acid) (PLA), and PLGA itself. In practice, such an embodimentof resorbable device 100 may be bent open to fit within engagementcatheter 700, and pushed into position using shaft 304 and/or embolus308. After resorbable device 100 has engaged tissue and/or organ 310 asshown in FIG. 8C (by way of a resorbable anchor portion 104), removal ofdelivery system 300 away from resorbable device 100 may allow resorbabledevice 100, as shown in the embodiment shown in FIG. 8A, to bend backinto its natural/native configuration, allowing a second resorbableanchor portion 104 to engage tissue and/or organ 310. Such a deliverymay then allow drug release portion 102 to deliver a drug over time asdescribed herein.

FIG. 9C shows a cross-sectional view of an embodiment of a deliverysystem 300 of the disclosure of the present application used to positiona resorbable device 100 of the present application having a chipconfiguration as shown in FIGS. 9A and 9B. As shown in the exemplaryembodiment shown in FIG. 9C, delivery system 300 comprises an engagementcatheter 700 having an optional skirt 702, a shaft 304, and an optionalembolus 308, whereby delivery system 300 is used to position aresorbable device 100 upon a tissue and/or organ 310. When shaft 304 hasbeen extended toward the distal end of engagement catheter 700,resorbable device 100 may be positioned at tissue and/or organ 310 asshown in FIG. 9B, whereby drug from the drug release portion 102 may bedelivered over time. In the embodiment of resorbable device 100 shown inFIGS. 9A-9C, resorbable device 100 comprises several resorbable anchorportions 104, noting that various embodiments of resorbable devices 100of the disclosure of the present application may have one or moreresorbable anchor positions 104.

FIG. 10A-10E show the resorption over time of an exemplary resorbabledevice 100 of the disclosure of the present application. FIG. 10A showsan exemplary embodiment of a resorbable device 100 having a drug releaseportion 102 positioned outside of a tissue and/or organ 310 and aresorbable anchor portion 104 positioned within a tissue and/or organ310. Over time, drug release portion 102 will begin to degrade anddeliver drug present within drug release portion 102 as shown in FIG.10B. FIG. 10C shows an embodiment of resorbable device 100 whereby drugrelease portion 102 has completely been absorbed by the body and alldrug within drug release portion 102 has been released. In at least oneexemplary embodiment as shown in FIG. 10D, after drug release portion102 has either partially or completely delivered the drug, resorbableanchor portion 104 will begin to degrade, and as shown in FIG. 10E, noportion of resorbable device 100 remains after drug release portion 102and resorbable anchor portion 104 has been absorbed/degraded by thebody.

FIGS. 11A and 11B show how an exemplary embodiment of a delivery system300 of the disclosure of the present application may be used to delivera resorbable device 100 of the present application to a septal wall of aheart. As shown in FIG. 11A and with the exemplary method stepsidentified in the method block diagram shown in FIG. 12, delivery system300 may be positioned within a blood vessel leading to a heart 1100 (anexemplary tissue and/or organ 310), further accessing heart 1100 (viathe pericardial space of the heart 1100, for example), to deliverresorbable device 100 as described herein. Prior to introducing thedelivery system 300 within the body at or near a target tissue or organ(introduction step 1204), an exemplary method 1200 of the presentapplication comprises the step of placing the resorbable device 100within a delivery tube 302 of delivery system 300 (placement step 1202).FIG. 11B shows an embodiment of a resorbable device 100 positionedwithin a heart 1100 at the septal wall 1102 of the heart 1100,positioned therein by, for example, performing the step of anchoring theresorbable device to the target tissue or organ (anchoring step 1206).The disclosure of the present application is not intended to be limitedto the delivery of only a pin 200 configuration of a resorbable device100 to the septal wall 1102 of a heart 1100, noting that any number ofconfigurations of a resorbable device 100 of the disclosure of thepresent application may be positioned within any number of tissuesand/or organs 310 within a body as described herein.

While various embodiments of devices, systems, and methods for localizeddrug delivery have been described in considerable detail herein, theembodiments are merely offered by way of non-limiting examples of thedisclosure described herein. It will therefore be understood thatvarious changes and modifications may be made, and equivalents may besubstituted for elements thereof, without departing from the scope ofthe disclosure. Indeed, this disclosure is not intended to be exhaustiveor to limit the scope of the disclosure.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described.Other sequences of steps may be possible. Therefore, the particularorder of the steps disclosed herein should not be construed aslimitations of the present disclosure. In addition, disclosure directedto a method and/or process should not be limited to the performance oftheir steps in the order written. Such sequences may be varied and stillremain within the scope of the present disclosure.

1. A method for localized drug delivery, the method comprising the stepof positioning a resorbable device within a pericardial spacesurrounding a heart of a mammalian body, wherein the resorbable devicecomprises: at least one drug release portion, comprising: at least onedrug to be released over time, and a binder intermixed with the at leastone drug; and at least one resorbable anchor portion forming the devicewith the at least one drug release portion and configured to activelyengage and anchor to a surface of the heart within the mammalian body.2. The method of claim 1, wherein the step of positioning the resorbabledevice within the mammalian body comprises the steps of: placing theresorbable device within a tube; introducing the tube into thepericardial space; and anchoring the resorbable device to the surface ofthe heart.
 3. The method of claim 2, wherein the step of anchoring theresorbable device to the surface of the heart is performed using a shaftpositioned within the tube.
 4. The method of claim 2, wherein the stepof anchoring the resorbable device to the surface of the heart isperformed using a gas from a gas source introduced into the tube tofacilitate placement of the resorbable device.
 5. A device for localizeddrug delivery, the device comprising: at least one drug release portioncomprising a binder and at least one drug, the binder biologicallydegradable within a mammalian body at a first rate of degradation; andat least one resorbable anchor portion forming the device with the atleast one drug release portion and configured to actively engage andanchor to a surface of a tissue or organ within the mammalian body, theat least one resorbable anchor portion biologically degradable withinthe mammalian body at a second rate of degradation that is slower thanthe first rate of degradation.
 6. The device of claim 5, wherein whenthe device is anchored to the surface of the tissue or organ within themammalian body, the at least one resorbable anchor portion maintains itsanchored position within the tissue or organ as the binder initiallydegrades and the at least one drug is released into the mammalian body.7. The device of claim 5, wherein when the device is positioned withinthe mammalian body, the at least one drug is released into the mammalianbody as the binder degrades at the first rate of degradation.
 8. Thedevice of claim 5, wherein the device comprises a configuration selectedfrom the group consisting of a pin configuration, a hook-pinconfiguration, a chip configuration, and a microchip configuration. 9.The device of claim 5, wherein the at least one resorbable anchorportion comprises at least one barb and at least one point-tip.
 10. Thedevice of claim 5, wherein the at least one resorbable anchor portioncomprises at least one coil.
 11. The device of claim 5, wherein thetissue or organ within the mammalian body comprises a mammalian heart.12. The device of claim 5, forming part of a system, the system furthercomprising: a tube having a proximal end and a distal end, the tubedefining a first opening at the proximal end and a second opening at thedistal end, the tube sized and shaped to facilitate placement of thedevice within the mammalian body by delivering the device from thesecond opening of the tube to a location within the mammalian body. 13.The device of claim 12, wherein the system further comprises a shaftpositioned within the tube, the shaft having a longitudinal axis, aproximal end, and a distal end, wherein the shaft is operable tofacilitate placement of the device within the mammalian body.
 14. Thedevice of claim 13, wherein the system further comprises an emboluspositioned at or near the distal end of the shaft, wherein the embolusis sized and shaped to facilitate placement of the device within themammalian body.
 15. The device of claim 13, wherein the shaft isrotatable about its longitudinal axis, and wherein the rotation of theshaft is operable to facilitate placement of the device within themammalian body.
 16. The device of claim 14, wherein the system furthercomprises a spring positioned at or near the distal end of the shaftbetween the shaft and the embolus, the spring capable to facilitateplacement of the device for localized drug delivery within the mammalianbody.
 17. The device of claim 12, wherein the tube comprises anengagement catheter.
 18. The device of claim 17, wherein the engagementcatheter comprises a skirt positioned at the distal end of theengagement catheter, the skirt operable to reversibly engage a tissue ororgan within the mammalian body to facilitate placement of the devicewithin the mammalian body.
 19. A device for localized drug delivery, thedevice comprising: at least one drug release portion comprising a binderand at least one drug, the binder biologically degradable within amammalian body at a first rate of degradation; and at least oneresorbable anchor portion forming the device with the at least one drugrelease portion and configured to fit within a pericardial spacesurrounding a heart and to actively engage and anchor to a surface ofthe heart, the at least one resorbable anchor portion biologicallydegradable within the mammalian body at a second rate of degradationthat is slower than the first rate of degradation.
 20. The device ofclaim 19, forming part of a system, the system further comprising: atube having a proximal end and a distal end, the tube defining a firstopening at the proximal end and a second opening at the distal end, thetube sized and shaped to facilitate placement of the device within thepericardial space by delivering the device from the second opening ofthe tube to a location within the pericardial space; and a shaftpositioned within the tube, the shaft having a longitudinal axis, aproximal end, and a distal end, wherein the shaft is operable tofacilitate placement of the device within the pericardial space.